Project Description Narrative:

Enterococci bacteria are among the three most common causes of hospital-acquired infection. Many of these infections are caused by multi-drug resistant enterococcal (MDRE), which render antibiotics ineffective. Antimicrobial resistance has been increasing rapidly. While the current approach has been to use multiple combinations of antibiotics, this may be ineffective and result in massive disruption of the intestinal microbiome. Using multiple combinations of antibiotics may also exacerbate the disease and cause secondary complications, such as increased susceptibility to intestinal and system infections, and increased local and systemic inflammation. Therefore, there is an urgent need for new approaches to address antibiotic-resistant infections.Through this award, researchers aim to prevent the emergency of such infections and reduce the spread of MDRE using targeted microbial therapy that will prevent undesirable collateral damage to the GI tract and preserve beneficial microbes that reside there.

Outcomes & Lessons Learned:

• Enabled research team to use a new approach for preventing and reducing MDRE infections• Documented progress toward testing a therapeutic strain of enterococcus that is capable of eliminating MDRE in GI tract of mice. This strain of bacteria has shown to be effective in vivo to eliminate enterococcal colonization and reduce enterococcal expansion• Began initial experiments to use enterococcal phages to decolonize enterococci from the gut, or to prevent expansion upon administration of antibiotics, establishing a phage dosing regimen that is capable of preventing enterococcal population expansion in the gut upon antibiotic administration. Attempts at decolonizing the gut of a target strain of E. faecalis have not yet been successful. Future experiments are planned.